Dopaminergic Control of the Explore-Exploit Tradeoff via Spiny Projection Neurons in the Striatum

项目摘要 为了有效地做出决策，个人必须利用他们的经验来平衡那些具有 已知的、积极的结果(开发)和选择，对备选方案进行抽样，以更好地估计比较的 当前选择(探索)的值。对这些基本状态的改变可能是 自闭症、强迫症等神经精神障碍的执行功能缺陷 精神障碍、多发性抽动症和成瘾。为了研究控制平衡的神经机制 在这两种状态之间，我们为小鼠产生了新颖的3-备选选择任务。我们将把这个作曲家 用尖端的病毒、遗传和成像工具来探测多巴胺是如何 与神经精神障碍相关的长期历史，调节着探索性和 剥削性行为状态。此外，我们还将进行单光子活体钙质成像。 纹状体中的神经元亚型，这是一个已知的管理决策的大脑区域，与 各种神经心理障碍。这个项目建立在一个重要的假设之上，该假设表明 纹状体活动的多巴胺能调节通过传递决定的价值来控制动作选择。这个 这项提议的目标是为我提供尖端实验技术方面的培训，如单光子 钙成像、病毒基因技术、决策的动力学模型和计算数据 分析。这些技术将使我能够经验性地测试多巴胺和纹状体神经元活动是如何组织的 探索性和剥削性行为状态下的决策。加州大学的Fuccillo实验室 宾夕法尼亚州已经证明了产生优秀研究和提供顶级培训的能力 对其成员来说，这使它非常适合这项提议。此外，拟议的工作将极大地受益于 为宾夕法尼亚大学的研究人员提供的设施和资源。

Project Summary In order to effectively make decisions, individuals must use their experiences to balance choices that have a known, positive outcome (exploitation) and choices that sample alternatives to better estimate the comparative value of the current selection (exploration). Altered regulation of these fundamental states may be central to executive function deficits apparent in neuropsychiatric disorders such as autism, obsessive compulsive disorder, Tourette’s syndrome and addiction. In order to study the neural mechanisms governing the balance between these two states, we generated novel 3-alternative choice task for mice. We will combine this operant behavior with cutting-edge viral, genetic and imaging tools to probe how dopamine, a neuromodulator that has a long history of association with neuropsychiatric disorders, regulates the expression of exploratory and exploitative behavioral states. In addition, we will perform 1-photon in vivo calcium imaging of spiny projection neuron subtypes in the striatum, a brain area known to govern decision-making and similarly associated with various neuropsychological disorders. This project builds off of a prominent hypothesis that suggests dopaminergic modulation of striatal activity governs action selection by conveying the value of decisions. The goal of this proposal is to provide me with training in cutting-edge experimental techniques such as 1-photon calcium imaging, viral-genetic technologies, dynamical models of decision-making, and computational data analysis. These techniques will allow me empirically test how dopamine and striatal neuron activity organize decision-making during exploratory and exploitative behavioral states. The Fuccillo Lab at the University of Pennsylvania has already demonstrated the ability to produce excellent research and provide premier training to its members, making it a great fit for this proposal. In addition, the proposed work will benefit greatly from all of the facilities and resources made available to researchers at the University of Pennsylvania.